The present invention relates to filtration devices, and in particular, couette membrane filtration systems for separating blood plasma from whole blood.
In the filtration and separation of fluid suspensions, devices using centrifugal effects exclusively, shearing effects in combination with membrane filtration and a combination of centrifugal and shearing action have been utilized. Devices utilizing centrifugal forces for achieving separation have been used with suspensions containing sedimenting components. Fluid suspensions, in general, have been filtered by means of membrane filtration devices. A particular type of membrane filtration device, one in which shearing effects are utilized to obtain filtration, is the couette membrane filter. A couette filter is one which is usually characterized by a series of laminar rotating, cylindrical sheets of fluid slipping over one another immediately adjacent a rotating surface. However, a couette filter can also include Taylor vortices without detracting from its ability to filter suspensions so long as the vortices are of laminar character.
In the usual configuration, a couette membrane filtration device utilizes a stationary cylindrical container and a cylindrical insert rotatably disposed within the container. The insert typically includes a semipermeable membrane wrapped around and supported by the insert. The stationary container and insert are dimensioned such that a narrow gap is defined between the inner facing surface of the container and the outer facing surface of the membrane. It is into this gap that the fluid suspension to be filtered is introduced. In this configuration, if the rotation speed is high enough, the laminar flow of cylindrical sheets is replaced by a laminar flow of a slightly different nature, one which is characterized by a regular sequence of counter-rotating toroidal vortices, i.e., Taylor vortices located in the gap. Provided the rotational velocity of the cylindrical insert is maintained below a certain upper limit, the toroidal vortices retain their individually laminar nature and occur as an alternating sequence of counter-rotating toroids which are located in the gap and appear regularly over the entire axial length of the rotatable insert. Such Taylor vortex flow is further characterized by a laminar fluid boundary layer located adjacent the membrane which retains a cylindrical shearing effect for a finite distance extending from the membrane surface radially into the fluid in the gap.
A dimensionless number, analogous to the Reynolds number, has been defined to characterize this flow and is referred to as the Taylor number. The Taylor number is related to the radius and speed of rotation of the insert, the gap thickness, and the viscosity of the fluid suspension. According to the classical definition of laminar flow, Taylor flow, for a Taylor number below known limits, can be considered to be laminar, since the fluid particles follow steady streamlines.
In use, the fluid suspension is introduced into the gap between the facing surfaces and caused to flow along and parallel to the membrane surface. Rotational motion between the insert and container is introduced by spinning the insert within the cylindrical container. The relative rotational motion of the two surfaces creates a rotational shearing action and the Taylor flow referred to above, which flows are superimposed on each other. By providing a sufficiently high shear rate, " . . . the gel layer of congealed solute, or the concentrated polarization layer of particles adjacent the membrane is swept away," as described by Lopez. The boundary layer is then characterized by a concentration gradient of suspended material that increases from nominally zero concentration at the membrane surface to the actual bulk concentration values of the fluid suspension in the region just beyond the laminar boundary layer.
The creation of an essentially particle-free boundary immediately adjacent to the membrane proceeds from a resolution of opposing forces Hydrodynamic forces, tending to drive particles of any density away from the membrane surface, are due to the fluid shearing action. These forces have the effect of being repulsive relative to either the rotating or stationary surfaces. Filtration drag produces convective forces acting in the opposite direction. Such drag is due to filtrate passing over the suspended particle, which must be left behind, as filtrate passes through the membrane (a particle may be any enclosed viscous discontinuity relative to the suspending medium, e.g., a bubble). Both forces act at right angles to the flow of the fluid suspension. The shearing repulsive force and the convective drag force exerted on the suspended particle are distinct from the pressure forces that drive the suspension along the membrane or the filtrate toward and through the membrane. Where the repulsive shearing force overbalances the convective drag forces, the particle-free boundary layer results. If pressure is now applied to the fluid suspension, a differential pressure, referred to as transmembrane pressure, TMP, exists across the membrane. The transmembrane pressure causes the now-separated fluid in the vicinity of the membrane to flow through the pores of the semipermeable membrane and onto the surface of the insert. The separated (filtered) fluid is then driven by pressure to an outlet from the device where it is collected. The balance of the fluid suspension with its now-increased concentration of suspended material flows within the gap under the influence of pressure and/or gravity to a second outlet of the unit where it is removed.
Such a device can be utilized for the separation of red blood cells from blood plasma in settings such as in blood donor centers. In the typical operation of a plasma donor center, the extraction of blood plasma is the important objective and the plasma is the material which is retained by the center typically for later use as plasma or for further processing to extract certain factors from the plasma. The donor's red blood cells, which are collected at the second outlet from the filtration device, are then reintroduced into the donor's circulation sometimes utilizing an additional saline solution as a suspending medium to provide the necessary fluidity and restore donor blood volume.
A limiting factor in the efficient operation of membrane filtration devices, particularly when used with blood, is the tendency of such filters to experience a phenomenon (polarization) wherein the pores of the semipermeable membrane become plugged with the red blood cells from the blood suspension to the point where the transmembrane flow of plasma is drastically reduced.
One reaction to this phenomenon has been an attempt to increase the pressure exerted on the fluid suspension introduced into the filtration device in an effort to force the plasma through the plugged membrane. Such efforts have been unsuccessful, however, since increases in transmembrane pressure merely cause more red blood cells to plug the pores of the filter increasing the resistance of the coated membrane to the flow of plasma therethrough.
It has been thought that a rotating filter type of device is the indicated solution to such a problem. In the configuration where the interior member is arranged to rotate within the hollow container, the unplugging or unfouling of the filter is sought to be accomplished by a combination of centrifugal action which tends to throw the plugging matter off of the surface of the rotating inner element where it is swept away by the "shearing" action that is created by the combination of the flow of fluid in the gap between the two elements and the relative motion of the two elements to each other.
Such an approach is described in U.S. Pat. No. 3,750,885 which is a strainer device having a rotatable cylindrical screen filter. Particles in the fluid suspension that build up on the screen filter are said to be removed from the outside of the screen by a combination of centrifugal and shear action. The filter apparatus described in the '855 patent provides for rotation of the interior screen section such that a centrifugal type of reverse flow can act together with a "shear" effect to dislodge particles from the screen surface. The centrifugal forces generated on the particles produce an outward radial dislodgement of the collected particles from the screen and removal from the screen. This approach is useful with heavier high density particles, but it has been shown in the scientific literature that centrifugal effects on nearly neutrally buoyant particles, such as red blood cells, are completely masked by shearing effects when the shearing effects are at a level to be useful for filtration.
Use of shearing effects to specifically obtain filtration of blood is described in U.S. Pat. No. 3,705,100 to Blatt. As described therein, the use of shearing effects on blood results in an improvement in the efficiency of the flow of plasma through the membrane. This approach has been used in later channel-type devices where an attempt has been made to achieve large membrane areas having relatively high rates of shear so as to obtain devices which are sufficiently efficient to obtain rates of flow which make the devices suitable for use in clinical settings such as blood donor centers. However, in the case of blood donor centers, the donor's natural blood flow rate is usually too low to achieve sufficiently high rates of shear and large membrane areas simultaneously.
A solution to this problem is provided in U.S. Pat. No. 4,212,742, wherein the concept of recirculation of the blood through the device is introduced. However, with or without recirculation, the viscosity of blood is such that the very high shear rates suggested by Blatt, viz., in excess of 2000 sec..sup.-1, cannot be achieved unless high driving pressure is employed as well. Consequently, there exists an unacceptably high TMP and associated polarization described earlier which cannot be mitigated because of the operation of physical principals governing flow under these conditions. This polarization problem is further compounded in that the deposition of red blood cells on the membrane causes severe damage to the cells, making the red blood cells unsuitable for return to the donor.
Others have taken the approach of accepting much lower rates of shear compensated by a very much increased membrane area, it being understood that less shear is accompanied by substantially lower permeate flux rates per unit of membrane area. This approach works better than the high shear method because the additional membrane required bears a non-linear, i.e., power less than one, relationship to the lowering of shear rate and permits the same total permeate flux for the device as a whole to be achieved with less driving pressure. Nevertheless, the membrane areas required in this case are very large and costly, rendering the device prohibitive for some uses such as donor plasma collection or large-scale therapeutic apheresis.
Still another consideration that must be taken into account in the design of either a couette type filter or channel device is the fact that, as such devices are used with blood, and plasma is extracted as the whole blood flows through the device, the extraction of plasma results in an increasing cell concentration, i.e., hematocrit of the remaining concentrated blood. Not only does viscosity increase rapidly with increasing hematocrit, but it can also be seen that the tendency of the exit portion of the filter to become plugged also increases markedly. Both the increase in viscosity and filter plugging contribute to blood cell damage.